Crosslinking of collagen scaffolds promotes blood and lymphatic vascular stability

The low stiffness of reconstituted collagen hydrogels has limited their use as scaffolds for engineering implantable tissues. Although chemical crosslinking has been used to stiffen collagen and protect it against enzymatic degradation in vivo, it remains unclear how crosslinking alters the vascular...

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Bibliographic Details
Published in:Journal of biomedical materials research. Part A 2014-09, Vol.102 (9), p.3186-3195
Main Authors: Chan, Kelvin L. S., Khankhel, Aimal H., Thompson, Rebecca L., Coisman, Brent J., Wong, Keith H. K., Truslow, James G., Tien, Joe
Format: Article
Language:English
Subjects:
Biocompatible Materials - chemistry
Biological and medical sciences
Biomedical materials
Bioprosthesis
Biotechnology
Cell Line
Collagen - chemistry
Collagens
Cross-Linking Reagents - chemistry
Crosslinking
Endothelial Cells - cytology
Ethyldimethylaminopropyl Carbodiimide - chemistry
extracellular matrix
Fundamental and applied biological sciences. Psychology
Gels
Health. Pharmaceutical industry
Humans
Hydrogels
Industrial applications and implications. Economical aspects
Iridoids - chemistry
Materials Testing
Medical sciences
microvascular tissue engineering
Miscellaneous
perfusion
Scaffolds
Stability
stiffness
Stress, Mechanical
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Surgical implants
Technology. Biomaterials. Equipments
Tissue Scaffolds - chemistry
Tubes
vascular physiology
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Summary:The low stiffness of reconstituted collagen hydrogels has limited their use as scaffolds for engineering implantable tissues. Although chemical crosslinking has been used to stiffen collagen and protect it against enzymatic degradation in vivo, it remains unclear how crosslinking alters the vascularization of collagen hydrogels. In this study, we examine how the crosslinking agents genipin and 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide alter vascular stability and function in microfluidic type I collagen gels in vitro. Under moderate perfusion (∼10 dyn/cm2 shear stress), tubes of blood endothelial cells (ECs) exhibited indistinguishable stability and barrier function in untreated and crosslinked scaffolds. Surprisingly, under low perfusion (∼5 dyn/cm2 shear stress) or nearly zero transmural pressure, microvessels in crosslinked scaffolds remained stable, while those in untreated gels rapidly delaminated and became poorly perfused. Similarly, tubes of lymphatic ECs under intermittent flow were more stable in crosslinked gels than in untreated ones. These effects correlated well with the degree of mechanical stiffening, as predicted by analysis of fracture energies at the cell–scaffold interface. This work demonstrates that crosslinking of collagen scaffolds does not hinder normal EC physiology; instead, crosslinked scaffolds promote vascular stability. Thus, routine crosslinking of scaffolds may assist in vascularization of engineered tissues. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3186–3195, 2014.
ISSN:1549-3296
1552-4965
DOI:10.1002/jbm.a.34990